Immune human sera were used to select a cDNA clone expressing an asexual blood-stage antigen of Plasmodium falciparum. Antibodies affinity-purified on extracts from this clone were used to characterize the antigen by immunoblotting and immunofluorescence. The antigen is present in mature-stage parasites as a high molecular weight protein of about 250 kDa and is apparently processed to smaller fragments in the merozoite. It varies in molecular weight and antibody reactivity in different isolates, and has been localized at the erythrocyte membrane by immunoelectronmicroscopy. Part of the protein is composed of exactly repeated hexapeptide units that constitute the strain-specific determinant. This molecule has similar characteristics to the strain-specific molecule believed to be responsible for cytoadherence.